1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)-octane and processes for its preparation



United States Patent M 1-HYDROXYMETHYL 6,8 DIOXABICYCLO(3.2.1)- OCTANE AND PROCESSES FOR ITS PREPARA- TION Andrew P. Dunlop, Riverside, and Daniel S. P. Eftax,

Barrington, Ill., assignors to The Quaker Oats Company, Chicago, 111., a corporation of New Jersey N0 Drawing. Original application Mar. 30, 1959, Ser. No. 802,652, now Patent No. 2,980,703, dated Apr. 18, 1961. Divided and this application Jan. 10, 1961, Ser. No. 81,681

4 Claims. (Cl. 260-3403) This application is a division of our previous application Serial No. 802,652, filed March 30, 1959, entitled 2,2 Bis(Hydroxymethyl)-3,4-Dihydropyran and Derivatives Thereof and Processes for Their Preparation, now Patent No. 2,980,703.

The subject matter of this and the aforementioned application Serial No. 802,652 relates to new and novel compounds, and more particularly to 2.,2-bis(hydroxymethyl)-3,4-dihydropyran (hereinafter also referred to as Compound I), derivatives thereof, i.e., l-hydroxymethyl- 6,8-dioxabicyclo(3.2.1)octane (hereinafter also referred to as Compound 11) and 2,2-bis(hydroxymethyl)-tetrahydropyran (hereinafter also referred to as Compound III), and to processes for the preparation of these new compositions of matter. Compounds I and III and processes for preparation thereof are claimed in our aforementioned application Serial No. 802,652. Compound II and processes for the preparation thereof are claimed in this divisional application.

The novel compound, Compound I, has the chemical structure indicated below:

\O/ \CHZOH It is prepared by reaction of formaldehyde with 2-formyl- 3,4-dihydro(2H)-pyran (so-called acrolein dimer) in the presence of an alkaline condensing agent. Aorolein dimer is obtainable from the Shell Chemical Corporation and the Union Carbide Corporation.

In a more specific embodiment of this invention 2- formyl-3,4-dihydro(2H)pyran is slowly added to a mixture consisting of aqueous or aqueous-alcoholic fonmaldehyde and an alkaline condensing agent, the mixture being maintained at a low temperature, i.e., within the range of about C. to about 60 C. during this addition. After a relatively short reaction period, depending on the temperature employed and the yield desired, the product is recovered from the reaction mixture by conventional methods known to those skilled in the art, for example, by fractional distillation and/ or crystallization. If necessary, external cooling is used to keep the temperature from exceeding the aforesaid range in order to minimize side reactions which might impair completion of the desired reaction.

As the alkaline condensing agent in the above specific embodiment, sodium hydroxide is satisfactory, preferably in an amount providing a molar ratio of sodium hydroxide to 2-formyl-3,4-dihydro(2I-I)pyran of at least about 1:1. Other agents which are effective include lime, barium hydroxide, potassium hydroxide, other alkali metal and alkaline earth metal hydroxides, and basic ion-exchange resins, the amount employed preferably being sufficient to provide at least about one equivalent weight of alkaline agent per mole of 2-formyl-3,4-dihydro(2H)pyran.

The amount of formaldehyde employed in the aforesaid specific embodiment is preferably not less than about 2 moles per mole of the 2-formyl-3,4-dihydro(2H)pyran.

Compound I 3,047,585 Patented July 31, 1962 The aqueous solution of formaldehyde is preferably one containing about 5% to about 40% by weight of formaldehyde. In recovering the desired product from the reaction mixture, a variety of procedures will be readily apparent to those skilled in the art. Preferably the reaction mixture (previously neutralized with an acid such as formic acid, or as is) is concentrated, for example by distillation. The concentrate so obtained is diluted with any solvent for Compound I which is later easily separated therefrom (e.g., saturated low-boiling aliphatic alcohols and methyl isobutyl ketone). The resulting solid phase and liquid phase are separated. The desired product, Compound I, is then preferably recovered from the liquid phase by fractional distillation.

The following examples are illustrative of the preparation of Compound I, though not limiting inasmuch as many variations may be made therein without departing from the spirit or scope of the invention. Except as noted otherwise, all parts and percentages are by weight.

Example 1 One hundred and twelve parts of 2-formyl-3,4-dihydro- (2H)pyran was added incrementally over 1.5 hours to a mixture comprising 47.5 parts of sodium hydroxide in 155 parts of water and 202 parts of a 37% formaldehyde solution. The temperature during the addition was maintained at 20 C. and then kept below 30 C. for 2 additional hours. Following this period the mixture was heated to 55-60 C. and kept at that temperature for 3.25 hours. One-half of the reaction mixture was concentrated until solid matter (sodium fonmate) began to precipitate. The solids were filtered rinsed with isobutanol, and the rinsings combined with the filtrate and distilled under reduced pressure. In this way there was obtained 50 parts of the desired product, Compound I, boiling at 102.5109C./0.6-0.85 Hg. The other half of the reaction mixture was extracted four times with a total of about 200 parts of isobutanol. Distillation of the isobutanol extract under reduced pressure gave 52 parts of product, Compound I, boiling at 101107 C./ 0.350.6 mm. Hg. The combined yield was about 71% 0f the theoretical. The product, Compound I, was a colorless liquid which, when pure, crystallized on standing at room temperature. A purified sample, recrystallized from a benzene-Skellysolve B mixture, melted at 51-52 C., and analyzed 58.40% carbon and 8.29% hydrogen, compared to theoretical values of 58.31% carbon and 8.39% hydrogen. The bis-p-nitro-benzoic ester of Compound I was prepared as an identifying derivative. It melted at 138139 C., and analyzed 57.03% carbon, 4.16% hydrogen and 6.39% nitrogen compared to theoretical values of 57.01%, 4.10% and 6.33%, respectively.

Example 2 One hundred and twelve parts of the same 2-formyl- 3,4-dihydro(2H)-pyran as was employed in Example 1 was added to alkaline formaldehyde solution (same quan tities as in Example 1) over a period of 1.25 hours while keeping the temperature at about 20 C. during the addition and for 60 minutes thereafter. The mixture was stirred for an additional 1.5 hours during which period the temperature rose to a high of 29 C. Following this period, the mixture was heated to 52-60 C. for 2.5 hours and then allowed to stand for 40 hours at 25 C. The resulting reaction mixture was extracted five times with a total volume of about 280 parts of isobutanol and was then concentrated under reduced pressure causing the precipitation of sodium formate. The precipitate was filtered off and washed with isobutanol. The combined filtrate and isobutanol. used in washing were then further distilled to obtain further concentration. Final distillation gave a product, Compound I, boiling in the range of 105 111C./

0.5-0.9 mm. Hg. The yield was 119.5 parts or 83% of the theoretical.

Under acidic conditions, the new compound, Compound I, undergoes an intra-molecular addition reaction (intrareaction) to form the isomeric 1-hydroxymethyl-6,8-dioxabicyclo(3.2.l)-octane, Compound II, This is also a new composition of matter having the structure shown below:

(L H; Compound II A variety of acid-reacting substances catalyze the formation of Compound II from Compound I. Among these are the mineral acids and acid-reacting salts thereof, and the so-called Lewis acids. Carboxylic acids also catalyze the isomerization. The quantity of the acidic catalyst required is variable depending upon acid strength, rate of reaction desired, etc. A reaction solvent is preferably employed and includes such solvents for the starting materials as tetrahydrofuran, tetrahydropyran, ethyl ether and saturated low-boiling alcohols. The reaction mixture is preferably neutralized with a basic reactant prior to recovery of the desired product by conventional means such as fractional distillation. The following examples are illustrative:

Example 3 A solution of 14.4 parts of 2,2-bis(hydroxymethyl)3, 4-dihydropyran, Compound I, in 25 parts of ethyl ether was added with stirring to a solution of 0.34 part of boron trifluoride .in approximately 6 parts of ethyl ether over a period of 3 minutes. The temperature rose from 25 C. to 33 C., and remained there for minutes, after which the mixture was brought to reflux. After 2 hours with constant stirring, one part of concentrated ammonium hydroxide was added. The reaction mixture was then filtered and the ethyl ether removed by distillation. From the residual material, further distillation produced 13 parts of the desired product, Compound II, boiling at 54- 65 C. at 018-02 mm. Hg. A purified sample boiled at 45 C. at 0.05 mm. Hg, 11 1.4790, and analyzed 58.48% carbon and 8.31% hydrogen compared to the theoretical values of 58.31% carbon and 8.39% hydrogen. The product, Compound II, was a colorless liquid, the p-nitrobenzoic ester of which was prepared as an identifying derivative. This derivative melted at 94.5- 95 C. and gave an analysis of 57.27% carbon, 5.27% hydrogen and 4.91% nitrogen as compared to the theoretical values of 57.33%, 5.16%, and 4.78%, respectively.

Example 4 One drop of concentrated hydrochloric acid was added to a solution of 14.4 parts of 2,2-bis(hydroxymethyl)3, 4-dihydropyran, Compound I, in 20 parts of ethanol. The mixture was allowed to stand for 3 hours with occasional agitation after which period a few pellets of sodium hydroxide were added. The ethanol was removed under reduced pressure and final distillation produced 10.5 parts of the desired product, Compound 11, boiling at 63-5 C. at 0.375 mm. Hg and at 805-232 C. at 1.25 mm. Hg. The p-nitrobenzoic ester of this material melted at 94.5- 95 C. and showed no depression in melting point when mixed with the p-nitrobenzoic ester prepared in Example 3.

By saturating Compound I with hydrogen, there is obtained the new compound, 2,2-bis(hydroxymethyl)tetrahydropyran, Compound III, having the structure shown below:

CH; CH2 OH:

H; C HQOH 0 CHzOH Compound III Illustrating how these products may be employed in the preparation of antifreezes, mixtures composed of equal parts of water and 2,2-bis(hydroxymethyl)tetrahydropyran, Compound III, gave a satisfactory -15" C. freezing point. A mixture of equal parts of water and lhydroxymethyl-6,8-dioxabicyclo(3 .2.1 )octane, Compound 11, gave a freezing point of 9" C., while a mixture of equal parts of water and 2,2bis(hydroxymethyl)-3,4-dihydropyran, Compound I, gave a freezing point of 7 C.

These new products may also be used in the preparation of high temperature lubricants. Thus, the distearate of 2,2-bis(hydroxymethyl)tetrahydropyran, prepared in quantitative yield by heating 11 parts (0.075 mole) of 2,2- bis(hydroxymethyl)tetrahydropyran, Compound III, and 43 parts (0.15 mole) of stearic acid at temperatures up to 240 C. for 11 hours until 2.7 parts (0.15 mole) of water was collected, had a melting point of 46 C. and was stable to heating at elevated temperatures for long periods of time. Similarly, the stearate of 1-hydroxymethyl-6,8- dioxabicyclo( 3.2.1) octane, prepared by heating 13.2 parts (0.1 mole) of 2,2-bis(hydroxymethyl)-3,4-dihydropyran, Compound I, with 57 parts (0.2 mole) of stearic acid at temperatures up to 230 C. for 11 hours until 1.8 parts (0.1 mole) of water was collected (removing 29 parts (0.1 mole) of stearic acid by distillation under reduced pressure), melted at 36 C. and boiled at 1902l0 C. at 0.35 mm. Hg and showed the same stability to high temperatures for prolonged periods.

The new compounds of the invention have a number of uses in addition to that of being anti-freeze agents for pharmaceuticals and entering into the preparation of high temperature lubricants. The diacetate ester of 2,2-bis- (hydroxymethyl)tetrahydropyran, Compound III, is useful as a solvent for cosmetic preparations such as lipstick and nail polish.

Other valuable derivatives of 1-hydroxymethyl-6,8- dioxabicyclo(3.2.1)octane, Compound II, and 2,2-bis(hydroxymethyl)tetrahydropyran, Compound III, such as various ethers are unique as reaction solvents in systems involving boron halides and boron hydrides.

We claim:

1. 1-hydroxymethyl-6, 8-dioxabicyclo 3 .2. 1 octane.

2. A process for the preparation of l-hydroxymethyl- 6,8-dioxabicyclo( 3 .2. 1 octane which comprises intra-reacting 2,2-bis(hydroxymethyl)-3,4-dihydropyran in the presence of an acid reacting catalyst.

3. A process for preparing 1-hydroxymethyl-6,8-dioxabicyclo(3.2.l)octane, which comprises intra-reacting 2, 2-bis (hydroxymethyl)-3,4-dihydropyran dissolved in a solvent selected from the group consisting of tetrahydrofuran, tetrahydropyran, ethyl ether, and saturated lowboiling alcohols, in the presence of an acid catalyst; removing said acid agent by neutralization; and recovering the desired product from the reaction mixture by fractional distillation.

4. A process for preparing l-'hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane, which comprises intra-reacting 2,2- bis(hydroxymethyl)-3,4-dihydropyran dissolved in a solvent selected from the group consisting of tetrahydrofuran, tetrahydropyran, ethyl ether, and saturated lowboiling alcohols, in the presence of an acid catalyst; removing said acid agent by distillation; and recovering the desired product from the reaction mixture by fractional distillation.

No references cited. 

1. 1-HYDROXYMETHYL-6,8-DIOXABICYCLO(3.2.1)OCTANE. 